Neuromas develop as a part of a normal reparative process following peripheral nerve injury. They are formed when nerve recovery towards the distal nerve end or target organ fails and nerve fibers improperly and irregularly regenerate into the surrounding scar tissue. Neuromas consist of a deranged architecture of tangled axons, Schwann cells, endoneurial cells, and perineurial cells in a dense collagenous matrix with surrounding fibroblasts (Mackinnon S E et al. 1985. Alteration of neuroma formation by manipulation of its microenvironment. Plast Reconstr Surg. 76:345-53). The up-regulation of certain channels and receptors during neuroma development can also cause abnormal sensitivity and spontaneous activity of injured axons (Curtin C and Carroll I. 2009. Cutaneous neuroma physiology and its relationship to chronic pain. J. Hand Surg Am. 34:1334-6). Haphazardly arranged nerve fibers are known to produce abnormal activity that stimulates central neurons (Wall P D and Gutnick M. 1974. Ongoing activity in peripheral nerves; physiology and pharmacology of impulses originating from neuroma. Exp Neurol. 43:580-593). This ongoing activity can be enhanced by mechanical stimulation, for example, from the constantly rebuilt scar at the injury site (Nordin M et al. 1984. Ectopic sensory discharges and paresthesiae in patients with disorders of peripheral nerves, dorsal roots and dorsal columns. Pain. 20:231-245; Scadding J W. 1981. Development of ongoing activity, mechanosensitivity, and adrenaline sensitivity in severed peripheral nerve axons. Exp Neurol. 73:345-364).
Neuromas of the nerve stump are unavoidable consequences of nerve injury when the nerve is not, or cannot be, repaired and can result in debilitating pain. This is particularly likely if the neuroma is present at or near the surface as physical stimulation induces signaling in the nerve resulting in a sensation of pain.
Neuroma prevention and attenuation strategies have used various methods to limit the size of the neuroma and protect the neuroma from external stimuli. Current prevention methods, see FIG. 1, attempt to limit the size of the neuroma and so reduce or limit possible communications between axons within the injured nerve site by limiting the number of other axons and axons contacts in the disorganized structure that characterizes neuromas. Due to a variety of factors, current methods of neuroma mitigation/prevention have an unacceptable level of efficacy.
While various methods to prevent, minimize, or shield neuromas have been attempted, the current clinical “gold standard” for treating neuromas is to bury the nerve end (that will form the neuroma) into muscle or a hole drilled in bone. The surrounding tissue cushions and isolates the neuroma so that it is not stimulated (so it does not cause painful sensations). However this procedure can greatly complicate the surgery as significant additional dissection of otherwise healthy tissue is required to place the nerve stump. For these reasons, placement of the nerve stump is often not performed in amputations (and many other nerve procedures) despite the fact that ˜30% of neuromas become painful and problematic.
Another method used is to dissect the nerve stump back to leave a segment of epineurium overhanging and then ligate the overhanging epineurium, or covering the face of the nerve stump with the freed epineurium (or use a segment of the epineurium from the distal nerve). Yet another method that is commonly used today is a suture ligation. Basically, a loop of suture is placed around the end of the nerve and tightened. This pressure is then believed to mechanically block the exit of axons and eventually form scar tissue at the site. However clinical and pre-clinical evidence has shown that a painful neuroma can form behind a ligation. The ligated nerve is generally not positioned to minimize mechanical stimulation of the neuroma, though studies have shown that positioning the nerve in a protected area can resolve chronic stump pain.
Covering the nerve stump with a silicone rubber tube, a vein, or a silicone rubber plug (i.e. a tube with a sealed end) has also been used.
Current methods for addressing neuromas have not been generally successful and therefore not generally adopted.